Academic literature on the topic 'Measles WGS'

Background: Despite the availability of a safe and effective vaccine, measles remains endemic in many countries and is the main cause of morbidity and mortality among young children. Therefore, the main objective of the study was to investigate the immunological features of measles in children. Materials and Methods: The immune status of children (n = 72) who were diagnosed with measles, was analysed. Various lymphocyte proportions were determined using monoclonal antibodies and immunofluorescence microscopy. The immunoregulatory index was calculated. Results: The relative content of CD4+ and CD8+ T cells in the experimental group comprising of moderately and severely ill patients was significantly lower. The immunoregulatory index was reduced, and there was a positive correlation (0.3) between the indices during admission (2.0469 ± 0.04830) and during the entire hospital stay (1.9258 ± 0.09099) in moderately ill patients, respectively. The proportion of CD16+ T cells was higher at admission and the rate of the increase in CD16+ T cell proportion was significantly higher (P < 0.05). CD16+ counts were higher in moderate to severe cases. Thus, moderately and severely ill children with measles exhibited T-cell immune deficiency. Conclusion: The severity of measles directly correlated with the patient age, with the disease progressing to the severe status in younger children (r = -0.3).

In Western Pacific, the number of measles cases dropped precipitously in early 2020. As the coverage of measles vaccine remained almost unchanged, the precipitous drop of the measles cases could not be attributed to measles vaccine. It was probably brought about by physical distancing and other measures to prevent spread of SARS-CoV-2. SARS-CoV-2 cases increased wave by wave, while the number of the deaths divided by that of the patients declined. The decline of the casefatality rate could not be attributable to SARS-CoV-2 vaccine, because the trend emerged from the start of the epidemic, far ahead of introduction of SARS-CoV-2 vaccine.

Background:Despite efforts to promote widespread vaccination,measles stillremains an important cause of morbidity and mortality in children especially in developingcountries. The aim of this study was to review the pattern and outcome of measles patientsadmitted at Benazir Bhutto Hospital (BBH) Rawalpindi during measles epidemic 2013.StudyDesign: Cross sectional descriptive study. Period:Three months during measles epidemic 2013(March - May). Setting:Pediatric department BBH Rawalpindi. Materials and Methods:Dataregarding demographic profile, clinical presentation, complications and outcome of measlespatients was collected and analyzed using SPSS 15.Results:A total of 192 patients of bothsexes were included with mean age of 35.48+32.71 months. Majority of patients(71.4%) wereunvaccinated and 88% had history of contact with measles patients. The common complicationsobserved were pneumonia and pneumonia with gastroenteritis and both were found statisticallysignificant in patients with malnutrition and low socioeconomic status.Conclusion:The currentstudy concluded that improving measles immunization and nutritional status in children isessential for reducing morbidity and mortality of measles.

INTRODUZIONE. Il morbillo è una malattia esantematica estremamente contagiosa trasmissibile per via aerea causata da un virus della famiglia Paramyxoviridae, genere Morbillivirus. L’infezione spesso è causa di complicanze severe e decessi, è prevenibile con la vaccinazione e presenta i requisiti per l’eliminazione. L’Italia fa parte dei 12 paesi europei dove la trasmissione del morbillo è ancora endemica. Il Global Measles and Rubella Strategic Plan 2012 – 2020 ha fissato il goal di eliminazione del morbillo endemico nella Regione Europea dell’OMS. Per raggiungere tale obiettivo è necessario ottenere e mantenere coperture vaccinali elevate (>95%) e disporre di un sistema di sorveglianza sensibile e di qualità. La sorveglianza molecolare del morbillo è una componente chiave della verifica dell'eliminazione del morbillo endemico ed è uno strumento cruciale sia per stabilire eventuali link epidemiologici tra casi che si verificano nello stesso periodo in una determinata area geografica sia per identificare le possibili fonti di importazione. Con il progredire del programma di eliminazione, la diversità genetica dei ceppi di morbillo circolanti diminuisce. I continui viaggi aerei e la facilità di scambi tra i paesi favoriscono le importazioni in una determinata area geografica di varianti virali appartenenti allo stesso genotipo. In questo contesto, i tradizionali metodi di laboratorio non consentono di distinguere la trasmissione endemica da eventi di importazione delle stesse varianti virali. Con il progredire del programma di vaccinazione, inoltre, una quota sempre più alta di casi di morbillo si verifica in soggetti vaccinati. Le nuove e avanzate tecnologie devono quindi permette di ampliare le conoscenze su questi aspetti e consentire di identificare ceppi potenzialmente in grado di eludere la risposta immunitaria. SCOPO. Scopo del presente progetto di dottorato è quello di studiare e sorvegliare nel tempo l’epidemiologia molecolare del morbillo in vista dell’obiettivo di eliminazione, attraverso lo sviluppo e l’utilizzo di metodologie innovative molecolari e bioinformatiche. La ricerca pertanto si propone di combinare il metodo epidemiologico tradizionale con le tecniche molecolari e bioinformatiche che la nuova era offre. Un ulteriore obiettivo è stato quello di studiare casi confermati di morbillo in soggetti precedentemente vaccinati, al fine di valutare il fallimento vaccinale e identificare eventuali mutanti escape a livello del gene H. MATERIALI E METODI. Sono stati analizzati i campioni biologici provenienti da pazienti con diagnosi sospetta di morbillo raccolti nell’ambito della Sistema di Sorveglianza Integrata Morbillo e Rosolia della Regione Lombardia (rete MoRoNET), da marzo 2017 a luglio 2019. I campioni sono stati sottoposti a estrazione dell'RNA e a test di Real Time RT-PCR per l’identificazione del genoma del virus del morbillo. Tutti i campioni risultati positivi sono stati sottoposti a retrotrascrizione e a successiva amplificazione genica della regione N-450 del virus del morbillo mediante nested RT-PCR per la caratterizzazione genotipica. Campioni di interesse (N=50) sono stati sottoposti ad amplificazione del gene virale H mediante due emi-nested PCR e ad amplificazione dell’intero genoma attraverso l’utilizzo di specifiche coppie di primer per l’amplificazione di 10 frammenti parzialmente sovrapposti. Gli amplificati sono stati sequenziati e sono state analizzate filogeneticamente le sequenze N-450, N-450/H e l’intero genoma attraverso diversi programmi bioinformatici (ClustalX2, BioEdit, MEGA7) per le valutazioni filogenetiche. Lo studio dei casi vaccinati è stato condotto attraverso l’analisi dei dati sierologici ottenuti dal database del laboratorio di riferimento regionale; in aggiunta, è stata analizzata la sequenza amminoacidica (ottenuta tramite la conversione delle sequenze nucleotidiche grazie al programma BioEdit) della proteina H di 7 casi vaccinati e di 80 casi non vaccinati come gruppo controllo. I dati anagrafici, clinici ed epidemiologici relativi ai casi di morbillo analizzati nel presente lavoro sono stati ottenuti dal database della Regione Lombardia per le malattie infettive MAINF. RISULTATI. Complessivamente, tra marzo 2017 e luglio 2019 sono stati indagati 885 casi sospetti di morbillo segnalati a Milano e nelle aree limitrofe. Il 74.2% dei casi indagati è stato confermato in laboratorio. Il maggior numero di casi è stato confermato nel 2017 (50.4%). Le fasce d’età più colpite sono state quelle dei giovani tra i 15 e i 39 anni (63.0%) e degli adulti over-39 anni (21.5%), dato che si è confermato per tutti e tre gli anni esaminati. Il 92.1% dei casi confermati di morbillo non era vaccinato. La consultazione del database regionale MAINF ha permesso di classificare i casi confermati come sporadici (57.4%) o appartenenti a focolai (42.7%). Il 9.7% dei casi confermati dal nostro laboratorio si trovava fuori dal territorio in esame durante il periodo di incubazione della malattia. In questo modo è stato possibile definire l’importazione dell’infezione, sia dall’estero (44.3% dei casi importati) che da altre regioni italiane (55.7% dei casi importati). La caratterizzazione genotipica mediante sequenziamento della regione N-450 di Morbillivirus è stata completata con successo per il 95.3% dei casi. È stato possibile evidenziare la costante co-circolazione di due genotipi, il D8 (72.9%) e il B3 (26.1%). L’analisi intra-genotipica ha permesso di identificare complessivamente 16 varianti virali, di cui 8 già classificate dall’OMS e definite WHO named strain. In particolare, sono state identificate 5 WHO named strain D8 (Mv/Osaka.JPN/29.15, Mvs/London.GBR/21.16/2, MVi/Hulu-Langat.MYS/26.11, MVs/Gir-Somnath.IND/42.16, Mvs/Victoria.AUS/6.18) e 3 WHO named strain B3 (MV/Dublin.IRL/8.16, MVs/Saint-Denis.FRA/36.17, Mvs/Ljubljana.SVN.27.17). La D8-Osaka è stata la variante predominante nel 2017, la B3-Dublino nel 2018 e la D8-Gir Somnath nel 2019. Sono state inoltre identificate 69 sequenze non ancora classificate dall’OMS e momentaneamente denominate “no named strain”. Venti erano di genotipo D8 e 49 di genotipo B3. Alcune di queste sequenze hanno dato origine a eventi di trasmissione continua, altre a casi sporadici o a piccoli focolai familiari non propagandosi ulteriormente nella popolazione. È stata approfondita l’analisi molecolare di ceppi correlati a importanti eventi epidemici (focolai nosocomiali e familiari) e a casi notificati come sporadici avvenuti a breve distanza geografica e temporale dai focolai. È stato quindi sviluppato il sequenziamento e l’analisi filogenetica di una regione di più di 2000 nucleotidi, comprendente l’N-450 e tutto il gene H (N-450/H). Ciò ha reso possibile valutare la variabilità genetica (intra-variante) di ceppi 100% identici in N-450. L’analisi filogenetica di questa regione ha permesso di osservare che sequenze tra loro identiche nella sola regione N-450 formavano dei cluster e altre invece risultavano non strettamente correlate. In un secondo momento, gli stessi ceppi sono stati sottoposti a sequenziamento dell’intero genoma, la cui analisi filogenetica ha confermato i dati ottenuti in N-450/H, ma raggiungendo un maggior match con l’indagine epidemiologica e risultando più sensibile nel delineare le singole catene di trasmissione. È stato studiato il profilo sierologico di 33 casi confermati di morbillo con storia di vaccinazione documentata nel database regionale MAINF. Nel 18.2% dei casi, il riscontro di negatività in IgG in fase acuta (7-10 giorni dall’esordio del rash) ha suggerito una mancata risposta al vaccino (non-responder) e quindi un fallimento primario della vaccinazione. La gran parte dei casi vaccinati (81.8%) ha mostrato una risposta in IgG in fase acuta e pertanto inquadrabile come fallimento verosimilmente secondario. La capacità di trasmettere l’infezione da parte di soggetti con fallimento vaccinale è stata dimostrata nel 12% dei casi. Infine, i soggetti con fallimento primario avevano un’età mediana all’epoca dell’ultima dose più elevata rispetto a quelli con fallimento secondario (12 anni e 6 anni rispettivamente). Un ulteriore obiettivo del presente progetto è stato quello di analizzare 87 sequenze amminoacidiche della proteina H (target principale degli anticorpi neutralizzanti) identificate in soggetti vaccinati e non vaccinati. Di queste, 30, di cui 7 appartenenti a ceppi di casi vaccinati, presentavano sostituzioni in siti immunoepitopici. Le sostituzioni riscontrate sono state L247S, P247S, A400V, A192T e Q575K. Non sono invece state riscontrate mutazioni in siti funzionali della proteina, come per esempio residui di cisteina importanti per il mantenimento della struttura terziaria, o in siti di legame col recettore, responsabili del riconoscimento e dell’ingresso nella cellula ospite. CONCLUSIONI. L’andamento epidemiologico e genotipico dei casi di morbillo identificato nei 3 anni di studio a Milano e nelle aree limitrofe rispecchia quello riscontrato sul territorio nazionale. L’analisi intra-genotipica condotta ha permesso di identificare complessivamente 16 varianti virali, di cui 4 predominanti e un’elevata variabilità per entrambi i genotipi individuati (D8 e B3). Ciò conferma il pattern tipico nelle aree caratterizzate da un abbassamento delle coperture vaccinali e un aumento dei soggetti suscettibili alla malattia. Per dimostrare l’interruzione della circolazione all’interno del proprio territorio, i paesi devono essere in grado di distinguere le trasmissioni endemiche dai casi importati, in quanto la malattia può essere considerata eliminata solo in assenza di focolai endemici. La circolazione a livello mondiale di un ristretto numero di varianti virali limita l’informazione data dall’analisi filogenetica della regione N-450 e rende più complessa la ricostruzione delle rotte di trasmissione e la caratterizzazione dei focolai epidemici. Inoltre, non consente di ricostruire le catene di trasmissione e identificare i casi di importazione da fonti diverse. È pertanto importante mettere in atto nuove strategie metodologiche per ampliare la “finestra di sequenziamento”. L’analisi dell’intero genoma è risultata sensibile e in grado di ricostruire le catene di trasmissione e identificare i casi di importazione. Questa tecnica risulta tuttavia estremamente laboriosa e costosa e, nell’attuale contesto epidemiologico, non applicabile come metodica di routine. Potrebbe risultare invece la strategia ottimale per i paesi measles-free o che si stanno avvicinando all'eliminazione del morbillo, dove è necessario verificare l’introduzione solo di pochi ceppi virali. I risultati ottenuti nel corso dei 3 anni di dottorato sui ceppi coinvolti in importanti eventi epidemici a Milano e nelle aree limitrofe suggeriscono che l’analisi della regione N-450/H possa essere considerata una valida strategia di implementazione della sorveglianza molecolare in questa fase del programma di eliminazione. Per quanto riguarda lo studio dei casi confermati di morbillo in soggetti vaccinati, i risultati hanno dimostrato che la maggior parte dei fallimenti vaccinali non sono dovuti a una mancata risposta immunitaria (non-responder), ma piuttosto ad una perdita nel tempo della risposta immunologica vaccino-indotta. Tuttavia, la valutazione del titolo anticorpale è stata fatta durante la fase acuta della malattia e non si è potuto valutare quanti soggetti presentavano titoli anticorpali protettivi prima dell’infezione. Questa valutazione avrebbe contribuito a identificare i booster delle IgG in fase acuta causati dall’incontro col virus selvaggio. Il riscontro di una percentuale non trascurabile di casi di morbillo tra soggetti vaccinati che ha dato origine a focolai evidenzia la necessità di mantenere alta l’attenzione nel mettere in atto le misure di contenimento e diffusione della malattia anche in presenza di casi vaccinati. Ulteriori studi multidisciplinari devono essere condotti per confermare i risultati ottenuti e delineare opportuni piani risolutivi. L’analisi amminoacidica della proteina H ha permesso di identificare mutazioni in siti critici della proteina non osservate da studi precedenti. I dati ottenuti sono da un lato rassicuranti in quanto non mostrano la circolazione di mutanti escape, dall’altro documentano una variabilità della proteina H che impone la necessità di un monitoraggio costante. In conclusione, nel presente progetto di dottorato, sono state sviluppate e applicate metodologie innovative risultate utili per la corretta valutazione dello scenario epidemiologico attuale, caratterizzato dalla circolazione di ceppi endemici, dalla continua introduzione di varianti virali e da una quota non trascurabile di fallimenti vaccinali.
INTRODUCTION. Measles virus belongs to the morbillivirus genus of the family Paramyxoviridae. Infection with measles virus results in an extremely contagious exanthematic disease transmitted by air. It often causes severe complications and deaths, is preventable with vaccination and presents requirements for elimination. Italy is one of the 12 European countries where measles transmission is still endemic. The Global Measles and Rubella Strategic Plan 2012–2020 has set the goal of the elimination of endemic measles in the WHO European Region. To achieve this goal, high vaccination coverage must be obtained and maintained (>95%), and a sensitive and quality surveillance system must be ensured. Measles molecular surveillance is a key component to verify the endemic measles elimination, and a crucial tool both to establish any epidemiological link between cases occur in the same period and area, and to identify the importation sources. With the progress of the elimination program, the genetic diversity of circulating measles strains decreases. Continuous air travels and the ease world trade between countries facilitate imports into a given geographical area of viral variants belonging to the same genotype. In this context, traditional laboratory methods can not distinguish endemic transmission from import events of the same viral variant. In addition, as the vaccination program moves forward, an increasing proportion of measles cases occur in vaccinated individuals. New and advanced technologies must therefore allow us to broaden knowledge on measles in vaccinated people, and allow us to identify strains potentially capable of evading the immune response. AIM. The aim of the PhD project is to study and monitor in time the molecular epidemiology of measles in view of the elimination goal, through the develop and the use of innovative molecular and bioinformatic methodologies. Therefore, the research aims to combine the traditional epidemiological methods with the molecular and bioinformatic techniques of the new era. A further objective is to study measles confirmed cases in vaccinated people, in order to assess vaccination failure and to identify any escape mutant in the measles H gene. MATERIALS AND METHODS. From March 2017 to July 2019, biological specimens from patients with suspected measles were collected and analysed as part of the Measles and Rubella Integrated Surveillance System of the Lombardy Region (MoRoNET network). Viral RNA was extracted, and a Real Time RT-PCR was carried out for the measles genome identification. Retro-transcription was performed to all the measles positive samples, and a nested RT-PCR was conducted for the amplification of the N-450 region, in order to perform the genotyping. Samples of interest (N=50) have undergone two emi-nested PCR for the amplification of the H gene. Moreover, the amplification of the complete genome through specific couples of primers (which allow to obtain 10 overlapped fragments) has been conducted on the same samples. Amplicons were sequenced and a phylogenetic analysis was conducted on N-450 region, N-450/H region and on the whole genome, using the bioinformatic programs ClustalX2, BioEdit and MEGA7. Vaccinated measles cases were studied through analysis on serological data obtained from the regional referent laboratory database. In addition, the amino acid sequence of measles H protein (obtained from the conversion of the nucleotide sequences with BioEdit) was analysed in 7 vaccinated measles cases and 80 non-vaccinated measles cases, as control group. Personal, clinical and epidemiological data of measles cases analysed in this study were obtained from the Lombardy Region database of infectious diseases, MAINF. RESULTS. Overall, from March 2017 to July 2019, 885 suspected measles cases reported in Milan and surrounding areas were investigated. The 74.2% of measles cases was confirmed by laboratory investigations. The largest number of measles cases was confirmed in 2017 (50.4%). The age groups 15-39 years and over-39 years were the most affected over the all three years (63.0% and 42.7% of measles cases, respectively). The 92.1% of measles cases was unvaccinated. Regional database MAINF allowed to classify measles cases as sporadic (57.4%) or belonging to outbreaks (42.7%). The 9.7% of measles cases confirmed by our laboratory was outside the examined area during the incubation period of the disease. Genetic characterization was performed by the N-450 morbillivirus region sequencing and was completed with success in 95.3% of measles cases. The genotyping made possible to highlight the continuous co-circulation of two genotypes, D8 (72.9%) and B3 (26.1%). The intra-genotype analysis identified overall 16 viral variants, 8 of them already classified as WHO named strain. In particular, 5 WHO named strains D8 (Mv/Osaka.JPN/29.15, Mvs/London.GBR/21.16/2, MVi/Hulu-Langat.MYS/26.11, MVs/Gir-Somnath.IND/42.16, Mvs/Victoria.AUS/6.18) and 3 WHO named strains B3 (MV/Dublin.IRL/8.16, MVs/Saint-Denis.FRA/36.17, Mvs/Ljubljana.SVN.27.17) have been identified. The named strain D8-Osaka was the predominant genotype variant during the 2017. The named strain B3-Dublin was the predominant genotype variant during the 2018, and the named strain D8-Gir Somnath was the most frequently detected during the 2019. Moreover, 69 sequences not yet classified by the WHO have been identified and called “no-named strain”. Twenty no-named strains belonged to genotype D8 and 49 belonged to genotype B3. Some of them were responsible of continued transmission events, sporadic cases or small familiar outbreaks that did not further spread into the population. Molecular analysis has been deepened on strains correlated to nosocomial and familiar outbreaks and on strains correlated to sporadic cases occurred within short geographical and temporal distances from the outbreaks. It was therefore developed the sequencing and the phylogenetic analysis of a more than 2000 nucleotides region, which includes the N-450 region and the whole H gene (N-450/H). This made possible to evaluate the genetic variability of strains 100% identical in the N-450 region. Phylogenetic analysis of the N-450/H construct allowed to observe clusters within strains with the same N-450 region, whereas others 100% identical in N-450 were not strictly correlated. Subsequently, the whole genome sequencing was carried out on the same strains, and the phylogenetic analysis confirmed data obtained with N-450/H analysis. However, the whole genome sequencing analysis reached a greater match with the epidemiological investigation, and it resulted more sensitive outlining the single chains of transmission. The serological profile of 33 measles cases with a vaccination history was investigated. Negativity in IgG test during the acute phase of the disease (7-10 days from rash) was found in 18.2% of measles cases, suggesting a failure in vaccination response (non-responder) and therefore a primary vaccine failure. The majority of vaccinated measles cases (81.8%) showed an IgG response during the acute phase. Therefore, these cases could be placed in a secondary vaccine failure. Ability to transmit the infection to secondary cases was found in the 12% of vaccinated measles cases. In addition, the median age at the time of the last vaccine dose of measles cases with primary vaccine failure was higher than the one of measles cases with secondary vaccine failure (12 and 6 years old, respectively). Another goal of the present project was to analyse 87 aminoacidic sequences of measles H protein (first target of human neutralizing antibodies) identified in vaccinated and not vaccinated subjects. Of them, 30, of which 7 belonged to vaccinated measles cases, showed amino acid substitutions in antigenic epitopes. The substitutions were L247S, P247S, A400V, A192T, and Q575K. No mutations were found at functional sites of the protein, such as cysteine residues important for the maintenance of the tertiary protein structure, or on binding receptor sites, responsible for the recognition and the entry into the host cell. CONCLUSIONS. The epidemiological trend and genotypes of measles cases identified in Milan and the surrounding areas in the 3 years of study reflect what found on the national territory. The intra-genotyping analysis identified overall 16 viral variants, 4 of them predominant, and a high variability for both the D8 and B3 genotypes. This result confirms the typical pattern of areas characterized from a reduction of vaccination coverage and with an increment of susceptible subjects. To demonstrate the interruption of the virus circulation in the territory, countries must be able to distinguish endemic transmission form imported cases. Indeed, measles disease can be considered eliminated only in the absence of endemic outbreaks. The worldwide circulation of a small number of viral variants limits the information given by the phylogenetic analysis of the N-450 region, and makes more complex the reconstruction of transmission routes, as well as the outbreaks characterization. Furthermore, it is impossible to trace the chains of transmission and identify imported cases from different sources. It is therefore important to implement new methodologic strategies in order to extend the “window sequencing”. The whole genome analysis was sensitive and resulted able to trace the chains of transmission and identify the imported cases. This technique, however, is extremely laborious and expensive, and it is not applicable as routine tool in the actual epidemiological context. It could be instead the optimal strategy for measles-free countries, or for which ones is approaching the measles elimination, with only few cases to verify. The results obtained on strains involved in important epidemic events in Milan and surrounding areas during the 3-years PhD study suggest that the N-450/H analysis could be considered a good implementation strategy of the molecular surveillance in the actual elimination program phase. Regarding the study of measles cases in vaccinated subjects, it can be hypothesized that vaccination failure is not caused by an immunity system failure to vaccination (non-responder), but rather to a decline over the time of the immunity response vaccine-induced. However, the antibody evaluation was made during the acute phase of the disease, and it is not able to evaluate how many subjects had protective antibody titres before the infection. This evaluation would contribute to identified IgG boosters in acute phase caused by the wild-type measles strain exposure. The finding of an important proportion of vaccinated measles cases able to originate outbreaks highlight the necessity to maintain a high attention for the containment measures and for the spread disease control even in presence of vaccinated subjects. More multidisciplinary studies must be conducted to confirm the obtained results and to outline appropriate resolutive planes. Amino acid analysis of the measles H protein has led to identify mutations in critical protein sites observed for the first time. Data obtained are on the one hand reassuring because no escape mutant was found. On the other hand, data document a measles H protein variability which impose a constant monitoring. In conclusion, in this PhD project the innovative techniques developed and applied were found to be useful for the correct evaluation of the actual epidemiological scenario, which is characterized by the circulation of endemic measles strains, the continuous introduction of viral variants and a significant number of vaccine failures.

While memory is the faculty that affords us learning, adaptation and development, it is our executive function that oversees, manages and organizes these abilities. Still, there is limited research on the interaction between memory and executive function. The present study investigated this relationship through Principal Components Analysis. Performances on accepted measures of memory and executive function were evaluated in an adult clinical sample. Components were retained using three criteria: a predetermined four-component structure, eigenvalues exceeding a value of one, and parallel analysis. Results demonstrated that a four-component model most accurately represented the data. Analyses also revealed that measures of immediate and delayed memory did not uniquely assess memory but instead loaded onto components associated with visual and verbal processing. The findings were shown to be in support of the brain working in an integrated, systematic manner in which abilities hierarchically ascend from arousal to tertiary function. Consequently, several accepted measures of memory and executive function failed to measure cognitive capacity unique from visual and verbal processing, placing their construct validity and efficacy in question.

The aim of this study was to develop, digitally record, evaluate, and psychometrically equate a set of Spanish bisyllabic word lists to be used for word recognition testing. Frequently used bisyllabic words were selected and digitally recorded by male and female Spanish talkers. Twenty normally hearing subjects were presented each word to find the percentage of words which they could correctly recognize. Each word was measured at 10 intensity levels (-5 to 40 dB HL) in increments of 5 dB. Chisquare analysis was used to determine the equivalency among the final four psychometrically equivalent word lists of 50 words, and each of the eight half-lists containing 25 words each. The results of the analysis indicated that there were no significant differences among the four-lists or eight half-lists. Only minimal adjustments (≤0.5 dB) were needed to equate the words in the lists and half-lists for the male and female talkers.

AbstractThe worldwide increasing number of national guidelines and growing experience with realized green bank protections (constructions using insofar possible living or at least wooden construction material) in navigable waters, led to install a PIANC INCOM Working Group (WG) to collect and condense expert knowledge in this field of work and prepare it for practitioners for design purposes. The corresponding PIANC report, called “Technical-Biological Bank Protections for Inland Waterways”, is foreseen to be released this year.The report, whose structure, content, key findings and approach will be highlighted briefly in this contribution to the Smart Rivers Conference, tries to overcome the usual problems in design cases, which need knowledge and experience of civil engineers, eco-engineers and ecologists altogether and the way how the success of bank stabilization measures will be noticed and rated. The WG members had to notice that functionality assessment is not that simple, whereby partly huge differences between those who designed, realized and maintained measures and external parties as well as cultural differences occurred.To overcome these problems and thus to objectivize the choice and layout of alternative solutions, which may help to convince people responsible for waterway development and maintenance to use green measures instead of traditional bank protections as riprap, a Best Practice Approach was developed, based on a catalogue of numerous realized measures, which are described e.g. in so-called Fact Files. The content of these descriptions, especially the local boundary conditions (BCs shortly in the following) and the balance between aims and achieved functionality issues, was used to assess the possible suitability of a chosen measure under generally different design conditions than those in the described realizations.This was achieved inter alia by a scoring system, assessing differences between Design- (DC) and Analysis Cases (shortly ACs from the catalogue of measures), which is called Feasibility Check (it answers the question, whether experiences made with the AC-cases can be transferred to the DC) and differences between user-specified aims in the DC and expected performance issues from the ACs, called “Suitability Check” (answers the question, how far expected functionality issues may probably be achievable). This was done both for technical and ecological issues, whereby the scores were chosen and reviewed interdisciplinary and internationally to overcome the aforementioned assessment differences.

AbstractThe banking supervision in France was formalized with the Banking Acts of 1941 and of 1945. In 1941, the Banking Control Commission as the supervisory agency was created, and rigid financial regulation such as a minimum capital requirement and a separation of banking types was introduced. In connection to the 1941 Act, the four largest commercial banks in France were also nationalized. However, with the German occupation and the wartime situation, the formalization of banking supervision was only completed with the Banking Act of 1945. The essential contents of the 1941 Act were upheld, but the supervisory agency was given a lot of measures to enforce bank regulation. Especially, authorization of rigid penalties enhanced effectiveness of supervisory activities. The main drivers of the formalization of banking supervision in France were the policy measures undertaken during the Vichy regime and the Liberation Government's measures. In the post-Second World War era, the banking supervisory system was used mainly to enforce credit control policy actions, in a period of economic recovery and reconstruction. The banking act of January 1984 decompartmentalized the banking system and changed the institutions of supervision.

AbstractThe ‘new science of happiness’ was not really discovered, but was a coming together of people, publications, projects, politicians, agencies and disciplines around the turn of the twenty-first century. This moment foregrounded the issue of how people feel (subjective well-being), changing how this is understood and measured, driving the ‘second wave’ of well-being. This chapter reviews these interlinked histories to contextualise the ‘new’ well-being data. It presents definitions, theories and methods to help understand what went on behind the scenes and under the bonnet of these data practices. We look at the establishment of the UK’s subjective well-being measures and address the question of what subjective well-being can do that differs from previous well-being measures.

AbstractThrough more than 400 wells, tritium leakage of Pickering Nuclear Generating Station has been monitored seasonally since 1999. Sampling and maintenance of monitoring wells being costly, it is required limiting number of samples while ensuring monitoring objectives. This study aims at proposing a geostatistical approach for sample reduction while meeting the monitoring objectives. So, four objectives were defined: (i) Geographical coverage. (ii) Denser sampling where tritium variability is high. (iii) Delimiting the threshold of 300 kBq/L, also (iv) the cut-off of 3000 kBq/L. These objectives were quantified using geostatistical measures, served as cost functions in heuristic optimization algorithms, implemented using scripting capacity of Isatis.neo software. The algorithm was successful in sampling optimization of 2010Q4 (fourth season) according to the first, third and fourth measures. The first measure selects spatially evenly distributed wells, necessary for unknown leakages. The third and the fourth geostatistical measures suggest sampling around a decisive tritium concentration. Considering these objectives, 22 samples were removed (totally 50 samples) while deterioration of characterization accuracy is negligible. Temporal variogram revealed tritium correlation over three years. So previously acquired samples could be used to improve the monitoring in scarcely sampled areas. But sensitivity analysis showed that samples older than four seasons do not improve the current season contamination characterization. The conditional optimization was applied to samples of 2010 (all seasons). Previous samples improved the first and the last geostatistical measure, while deteriorated the second and the third measures.

<p>The non-engineered building built before 2004 remained after Gorkha earthquake although such structures demonstrate seismic deficient. Therefore, the present study aims to carry out detail seismic performance of such building to investigate as-built seismic performance and its performance after intervention of retrofit measures. Two in situ tests were performed, which includes Schmidt hammer test and ambient vibration test. The adaptive pushover analysis and dynamic time history analyses were performed for as-built and retrofitted building. The retrofit measures increase the stiffness and maximum base shear capacity of the buildings. In addition, such retrofit measures improved single storey drift concentration in existing building such that uniform drift profile can be attained. Furthermore, the probability of exceeding damage states can be significantly reduced and mainly found to be more effective in minimizing higher damage states, such as partial collapse and collapse states. The maximum expected annual loss occurs between 0.1 g and 0.2 g PGA (Peak Ground Acceleration). It was revealed that the steel braced building was found to be relatively more effective in enhancing the seismic performance, whereas reinforced concrete shear wall found more economic feasible retrofit measure for this particular building.</p>

This chapter explores the origin and infectivity of the measles virus in the course of human history. How measles first came to infect humans is not clear. Definitive proof is hard to come by since measles virus infection was once nearly impossible to distinguish from smallpox virus infection. Consequently, both had been lumped together as a single entity. As early as the tenth century, the Arab physician Abu Becr first attempted to distinguish between the two. However, it was not until the seventeenth century that English physician Thomas Sydenham actually documented the clinical entity of measles infection. Once it was understood that infection with measles virus confers lifelong protection from the disease and that humans are the natural host, interest turned toward developing a preventive vaccine. The chapter then considers the purported evidence that measles virus vaccines may be harmful. Such misinformation is often propagated for personal reasons yet greatly affects public health and individual lives.

There was a time when conducting research using documents meant spending months in a remote location sorting through filing cabinets in a basement. Today, though, websites, electronic databases, search tools, and digitization efforts have made organizational and governmental documents increasingly accessible. This chapter examines how such documents can be used in social science research examining religion using three illustrations from the author’s own work. One case looks at mission statements on congregational websites to assess variations in addressing openness to gay and lesbian individuals. Another example examines using newspaper archives to measure crimes against religious congregations. The third example illustrates the use of religious nonprofits’ tax returns to generate measures of finances, identity, and mission.

This paper intends to break down a local case to grasp the possibility of adaptable measures by individuals and systems through the social exchange during infrastructure interruption on account of considerable precipitation. Finally, the extent of social resilience is assessed through the ‘5S’ framework. The assessment reveals the social capital and the incredible social conditions accomplished by the mix of the particular circumstance and differing interest packs are influencing the adaptable appraisals which can be considered as an important report to structure a strong framework by understanding the tangled social issues and multifaceted nature

The construction sector can be identified as one of the highest energy-consuming industries in the world. The energy usage of the construction, operation, and maintenance stages is significant due to the complex nature of the industry. However, energy is one of the most undervalued resources in terms of efficiency and conservation in the construction stage. Higher energy usage and energy wastage in construction sites can be identified as significant matters, and various energy efficiency measures have massive potential for saving energy during the construction stage. Accordingly, this paper aims to investigate the sustainable use of energy practices on construction sites in Sri Lanka. A comprehensive literature review was conducted to identify principles and practices of sustainable use of energy, energy-using activities, processes, and the most applicable energy efficiency measures. The research aim was achieved through a qualitative research approach, and four case studies on building construction projects were conducted within the Colombo district. The case boundary of the study is defined as high-rise building sites. Semi-structured interviews, site observation, and document reviews were carried out as data collection techniques within each case. The collected data were analysed using manual content analysis. Key findings revealed how to use energy sustainably, what are the current energy sources and alternative sources available, construction activities and equipment used in the construction process, and reduce energy wastage by using energy efficiency measures. Rework, and workers’ behaviour highly affects the energy wastage on the site. Lack of planning, lack of information, limited space, and poor responses from the construction organisation were identified as the most relevant barriers that influence sustainable energy use on construction sites. The proposed recommendations for improving the sustainable use of energy should be adopted at the project level. Measures exceeding the scope of site management, industry-level support, and policy intervention are required.

Operational energy consumption in buildings has a crucial impact on global energy consumption. Nevertheless, significant energy savings can be achieved in buildings if properly designed, constructed, and operated. Building Energy Simulation (BES) plays a vital role in the design and optimisation of buildings. BES is used to compare the cost-effectiveness of energy-conservation measures in the design stage and assess various performance optimisation measures during the operational phase. However, there is a significant ‘performance gap’ between the predicted and the actual energy performance of buildings. This gap has reduced the trust and application of the BES. This article focused on investigating BES, reasons that lead to a performance gap between predicted and actual operational energy consumption of buildings, and the ways of minimising the gap. The article employed a comprehensive literature review as the research methodology. Findings revealed that reasons such as limited understanding of the building design, the complexity of the building design, poor commissioning, occupants’ behaviour, etc., influence the energy performance gap. After that, the strategies have been identified to minimise the energy performance gap such as proper commissioning, creating general models to observe occupants’ behaviour in buildings, and using the general models for energy simulation, ensuring better construction and quality through training and education, etc. Further, the findings of this study could be implemented by practitioners in the construction industry to effectively use energy simulation applications in designing energy-efficient and sustainable buildings.

severely due to the Corona Virus Disease (COVID-19) pandemic. Unbalance of the Irontriangle which refers to key Construction Project Goals (CPG) (i.e., time, cost, and quality) is one of the phenomena that can be addressed while Sustainable Development (SD) (i.e., economic, social, and environmental sustainability) has been streamlined to worse condition. Even though, sustainability must be prioritised in developing countries e.g., Sri Lanka, where significant construction works are currently underway, especially during this situation. Further, the appropriate construction and implementation in a construction project can make a dramatic contribution to the mandate of sustainable development. Hence, this research intends to investigate how the Iron triangle would be unbalanced during the new-normal situation where it has a significant impact on SD simultaneously. A qualitative survey strategy was used to achieve the research aim. A semi-structured interview survey was conducted to solicit the perception of experts. Nine experts were selected purposively, who had experience in both Sustainable Construction (SC) and project management, especially proceedings during the new-normal condition. To analyse the empirical data, the manual content analysis method was used. As the decisive outcome, the ‘Iron-star’ model was developed by merging the Sustainable triangle and Iron-triangle which pertained to the interrelation between SD and Construction Project Goals (CPG). Initially, interrelations between SD measures and CPG were cogitated by literature findings. Economic depletion, health-related issues, supply chain disruption, and cash flow issues were identified as interventions to achieve CPG through SD measures. Further, it revealed that the Iron-star can implement as the way forward for the construction industry in the Sri Lankan (SL) context.

Scope creep has been a day-to-day occurrence in almost every major road project causing a considerable cost overrun with no early dimple. This paper offers a critical appraisal on the dominant causes behind scope creep in the road projects. A comprehensive literature survey was undertaken to explore the factors specifically contributing scope creep and various control measures that are adopted, among other purposes, in at least reducing the impact due to scope creep in the final delivery of road projects. The study included interviews with 15 experts to identify major issues and add their hands-on experience. A questionnaire survey was subsequently administered among 100 industrial personnel having a cost management background in order to evaluate the effectiveness of the key performance indicators (KPIs) in terms of taming scope creep. Results from the study showed that concomitant client instructions on additional features, unclear scope and incremental changes cause scope creep throughout the project. Among 53 KPIs identified, the most effective KPI that enables adequate control of scope creep in road projects is the cost efficiency ratio. The results enable comprehending the causes of scope creep and its resultant net effect on cost control.

The purpose of this document is to provide readers with the coding protocol that authors used to code 96 studies that focused on Stages 1, 2, and/or 3 of curriculum-based measurement in mathematics (CBM-M) research. Stage 1 refers to evidence for using CBM at one point in time (i.e., static scores), such as for screening for difficulty. Stage 2 refers to evidence for using CBM repeatedly overtime, such as for progress monitoring. Stage 3 focuses on the instructional utility of CBM (i.e., instructional decisions to increase student achievement). The purpose of the systematic review was to update the Foegen et al., (2007) literature review on CBM-M. We evaluated 96 studies published since 2006 that included more than 540,000 participants. Nearly all studies (k = 83) reported results related to Stage 1, fewer studies reported results related to Stage 2 (k = 39) and Stage 3 (k = 4). The results of the systematic review report findings related to reliability, criterion validity, diagnostic accuracy, growth rates, and instructional utility of CBM-M.

In the article, the authors consider emergency situations at the enterprise of the Joint-Stock Company “Scientific and Production Complex “Alternative Energy” (JSC “NPK “ALTEN”), consider measures to prevent emergency situations at the enterprise, readiness to eliminate them consequences. Compliance with these measures will improve the efficiency of the company’s industrial safety management system. The relevance of the research is aimed at an effective system of organization and management of industrial safety, which allows you to manage risks and helps to ensure favorable working conditions for the health of employees at the enterprise. A mobile emergency and emergency response system was created. The system can also be used for accounting and accident investigation, based on the use of corporate communication devices and applications for mobile operating systems.

Evidence on the effectiveness of travel measures to prevent or slow the spread of Covid-19 and guidance on how and when to apply these measures is limited and the results are mixed. Given the social and economic disruptions that these measures can have, and their potential adverse effects on preventing the spread of the disease, WHO among others have cautioned implementing measures that are not supported by robust evidence. The scope of the search for this report was broad, covering all reported international travel restrictions to contain or slow the spread of Covid-19 and without geographical limitations. The results are therefore more general than restriction- or country-specific and more targeted studies may be omitted from the search due to these wide search parameters. There is general agreement across the literature that some form of travel restriction in the early stages of a disease or variant spread can lead to a slowing of the rate of infections in countries yet to be affected. The majority of studies conducted on travel restrictions adopt a modelling approach, and a systematic review conducted in December 2020 concluded that the quality of observational studies was low to very low (Bou-Karroum et al., 2021). Determining the specific effects of different travel measures is difficult as many studies examine the effects of combined measures. Few studies separate different types of restrictions and much of the modelling on international transmission rates uses data on the movements of people as a proxy for travel restrictions, therefore limiting the ability to observe how measures were implemented except for the timing of measures at different points in the pandemic. Limited country-level evidence was identified for this report and few global studies examine contextual factors that might affect the effectiveness of travel restriction measures. A targeted search for evidence on the effects of travel restrictions on different variants of Covid-19 did not reveal any studies making this distinction.

This brief sets out key considerations for risk communications and community engagement (RCCE) to promote adherence to COVID-19 preventive measures in greater Kampala, Uganda. It looks at adherence to COVID-19 preventive measures, assesses the challenges to their adoption and outlines key considerations for partners working in RCCE and the wider COVID-19 emergency response. The brief responds to concern (as of March 2022) about COVID-19 transmission in informal urban areas in Uganda due to their high population density, limited sanitary infrastructure, and reported low uptake of vaccination. Ensuring effective communication and engagement with a series of preventative measures is essential in limiting the spread of COVID-19. The Ministry of Health and response partners have been proactive, however interventions and guidance for COVID-19 have taken limited account of social science research about the perceptions and practices related to COVID-19 regulations. This brief aims to address this gap so these data may be used to inform more effective and practicable guidance for vulnerable groups. This brief draws primarily on an analysis of existing scientific and grey literature. Additional primary data was collected through consultation with six social science and RCCE experts who focus on this geographical area. The brief was requested by UNICEF Uganda in consultation with the Uganda Ministry of Health (MoH) RCCE subcommittee and the RCCE technical working group for the Eastern and South Africa region (ESAR). It was developed for SSHAP by Theresa Jones (Anthrologica) and supported by Elizabeth Storer (London School of Economics), with contributions and reviews by colleagues at Anthrologica, the Institute of Development Studies (IDS), UNICEF ESARO and Uganda, Makerere University, the London School of Hygiene and Tropical Medicine (LSHTM), Dreamline Products and the IFRC.

In road mitigation systems characterized by multiple wildlife crossing structures (CS) and multiple-focal species, these species-specific design criteria are important to meeting management goals. CS types and locations are fixed in place and cannot be manipulated experimentally; long term studies may offer the best chance to inform evidence-based designs for new CS projects in the future. Long-term data from Banff National Park are uniquely posed to answer these critical questions. More recently, highway mitigation along US93 in Montana provides an additional case study with which to understand the responses of large animals to different CS designs. The purpose of this study is to identify factors affecting movement of large mammals through CS using data sets from both mitigation projects. Year-round monitoring of CS use was used in an analytical framework to address questions regarding species-specific and community level use of CS; design and habitat factors that best explain species-specific variation; and whether importance of design parameters changes over time. Over the 17 years of the Banff study, and the six years of the Montana study, CS facilitated over 200,000 crossing events at 55 locations. There were significant changes in annual crossing events over time. Variables associated with CS passage rates were species specific, but aligned with a few clusters of preference. With the exception of coyotes, all large carnivore species preferred open span bridges or overpasses to other CS types. In Montana, fencing was positively associated with passage rates for black bears and cougars. We found that wider CS tend to be preferred by most species, irrespective of their location. We also found that wider CS tend to have shorter ‘adaptation’ curves than narrower ones for grizzly bears, coyotes, cougars, and moose. Depending on the heterogeneity of the landscape near the highway, more CS may not create more crossing opportunities if local habitat conditions do not favor animals’ access to the road. At the scale of ecological communities, the flows of mass and energy are likely enough to alter the distribution of ecological processes in the Banff and Montana ecosystems. Our results highlight the value of long-term monitoring for assessing the effectiveness of mitigation measures. Our work confirms the species-specific nature of measure CS performance, leading to our primary recommendation that a diversity of CS designs be considered an essential part of a well-designed mitigation system for the large mammals of western North America. Short-term monitoring efforts may fail to accurately portray the ecological benefits of mitigation for populations and ecological communities. Our results will help to inform design and aid in the establishment of robust, long-term performance measures.

The Illinois Marine Transportation System (IMTS) is a key component of the nation’s inland waterway system. IMTS is comprised of 27 locks and dams, 19 port districts, more than 350 active terminals, and 1,118 miles of navigable inland waterways traversing along the borderline or within the state of Illinois. However, the infrastructure of IMTS is aging and its conditions are deteriorating. To monitor the performance of IMTS and guide infrastructure investment to enhance safety, efficiency, and reliability of the system, a comprehensive performance measurement program is needed. To this end, the objective of this project is to create an integrated, comprehensive, and maintainable database that facilitates performance measurement of maritime freight to, from, and through Illinois. To achieve this objective, a review of the literature on maritime freight transportation both in the United States and abroad was performed. To gauge practitioners’ points of view, a series of phone interviews and online surveys of Illinois’ neighboring state DOT officials, officials from the US Army Corps of Engineers, Illinois port district authorities, and carriers operating in Illinois was also conducted. With the findings from the literature review and an understanding of state DOT practices, the needed and available data sources for a maritime freight performance measurement program were identified. Building on all the above efforts, a first-of-its-kind PM database for IMTS was designed and developed, along with a detailed user manual, ready for IDOT’s immediate use and future updates. In addition, opportunities for IDOT to use the database to conduct analysis are discussed. Key programmatic recommendations that outline the role of IDOT as a champion and as a facilitator are further included. The outcome of this project will help IDOT gain much-needed knowledge of and develop programs to improve IMTS performance, increase multimodal transportation network capacity, and expand the transportation and logistics sector of the state, which ultimately benefit the people and economy of Illinois.

In a recent research paper, we have proposed an extension of the lightweight Description Logic (DL) EL in which concepts can be defined in an approximate way. To this purpose, the notion of a graded membership function m, which instead of a Boolean membership value 0 or 1 yields a membership degree from the interval [0; 1], was introduced. Threshold concepts can then, for example, require that an individual belongs to a concept C with degree at least 0:8. Reasoning in the threshold DL T EL(m) obtained this way of course depends on the employed graded membership function m. The paper defines a specific such function, called deg, and determines the exact complexity of reasoning in T EL(deg). In addition, it shows how concept similarity measures (CSMs) ~ satisfying certain properties can be used to define graded membership functions m~, but it does not investigate the complexity of reasoning in the induced threshold DLs T EL(m~). In the present paper, we start filling this gap. In particular, we show that computability of ~ implies decidability of T EL(m~), and we introduce a class of CSMs for which reasoning in the induced threshold DLs has the same complexity as in T EL(deg).

Objective. The objective of this project was to demonstrate the feasibility and value of collecting harmonized depression outcome measures in the patient registry and health system settings, displaying the outcome measures to clinicians to support individual patient care and population health management, and using the resulting measures data to support patient-centered outcomes research (PCOR). Methods. The harmonized depression outcome measures selected for this project were response, remission, recurrence, suicide ideation and behavior, adverse effects of treatment, and death from suicide. The measures were calculated in the PRIME Registry, sponsored by the American Board of Family Medicine, and PsychPRO, sponsored by the American Psychiatric Association, and displayed on the registry dashboards for the participating pilot sites. At the conclusion of the data collection period (March 2020-March 2021), registry data were analyzed to describe implementation of measurement-based care and outcomes in the primary care and behavioral health care settings. To calculate and display the measures in the health system setting, a Substitutable Medical Apps, Reusable Technology (SMART) on Fast Healthcare Interoperability Resource (FHIR) application was developed and deployed at Baystate Health. Finally a stakeholder panel was convened to develop a prioritized research agenda for PCOR in depression and to provide feedback on the development of a data use and governance toolkit. Results. Calculation of the harmonized outcome measures within the PRIME Registry and PsychPRO was feasible, but technical and operational barriers needed to be overcome to ensure that relevant data were available and that the measures were meaningful to clinicians. Analysis of the registry data demonstrated that the harmonized outcome measures can be used to support PCOR across care settings and data sources. In the health system setting, this project demonstrated that it is technically and operationally feasible to use an open-source app to calculate and display the outcome measures in the clinician’s workflow. Finally, this project produced tools and resources to support future implementations of harmonized measures and use of the resulting data for research, including a prioritized research agenda and data use and governance toolkit. Conclusion. Standardization of outcome measures across patient registries and routine clinical care is an important step toward creating robust, national-level data infrastructure that could serve as the foundation for learning health systems, quality improvement initiatives, and research. This project demonstrated that it is feasible to calculate the harmonized outcome measures for depression in two patient registries and a health system setting, display the results to clinicians to support individual patient management and population health, and use the outcome measures data to support research. This project also assessed the value and burden of capturing the measures in different care settings and created standards-based tools and other resources to support future implementations of harmonized outcome measures in depression and other clinical areas. The findings and lessons learned from this project should serve as a roadmap to guide future implementations of harmonized outcome measures in depression and other clinical areas.

The objective of this study was to track trends in the signs of higher-quality addiction treatment as defined by the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Addiction, and the Substance Abuse and Mental Health Services Administration. We analyzed the National Survey of Substance Abuse Treatment Services from 2007 through 2017 to determine the percent of facilities having the characteristics of higher quality. We analyzed the percent by state and over time. • We found improvements between 2007 and 2017 on most measures, but performance on several measures remained low. • Most programs reported providing evidence-based behavioral therapies. • Half or fewer facilities offered medications for opioid use disorder; mental health assessments; testing for hepatitis C, HIV, and sexually transmitted diseases; self-help groups; employment assistance; and transportation assistance. • There was significant state-level variation across the measures.

Review question / Objective: Our goal will be to assess the impact on mental health of university students by comparing data from studies during and after contingency measures imposed to contain the spread of the SARS-CoV-2 coronavirus and to identify potential risk and protective factors for mental health. The results will be important for designing appropriate psychological interventions and mental health resources needed by university students. The research question was constructed following the PECO strategy. P=Population includes university students. E= exposure comprises contingency measures (confinement/social isolation/quarantine). C= comparison of studies conducted during and after the contingency measures (confinement/social isolation/quarantine) imposed by the pandemic of COVID-19. O= outcome immediate effect or consequences such as psychological impacts (depression, stress, anxiety, well-being, fear, burnout). Thus, the main question to be asked is: "What is the psychological impact caused by the Sars-Cov-2 pandemic on students' mental health during and after the contingency/restriction measures (confinement/social isolation/quarantine)?"